It is well known to those conversant with the physiology of perspiration that there are involved two distinct glandular species; the eccrine sweat glands and the aprocrine sweat glands. The eccrine sweat gland is found in generalized distribution over the human body surface with the average person having over two million glands. These glands produce water which contains salt and minerals, their main function being control of body temperature by evaporative cooling. The major quantity of sweat produced by the body is eccrine sweat.
The apocrine sweat gland is found primarily in the axillae and on the hair-covered regions of the body. The gland itself is somewhat larger than the eccrine sweat gland and generally opens into the hair follicle at a point above the level of the sebaceous gland opening rather than directly on the skin surface as does the eccrine gland. Apocrine sweat is a whitish, odorless liquid which contains considerable amounts of lipid materials as compared to eccrine sweat which contains over 99% water.
Up to the present time, the most widely used antiperspirant compositions intended for topical application to control the rate of eccrine perspiration have included a variety of metal salts capable of inhibiting the flow of perspiration by what has been described as an astringent action. These salts are thought to react with skin proteins, causing coagulation and concomitant swelling, resulting in the partial blockage of the external openings of the sweat gland and the reduction in the flow of sweat. In addition, these salts act as antimicrobial agents, preventing bacteria of the surface of the skin from acting on the lipid content of aprocine sweat to form objectionably odorous products.
In most of the commercial antiperspirant compositions on the market, the active antiperspirant ingredient is usually an astringent salt of aluminum, zinc, zirconium or rare earth metal. Such salts are generally not maximally effective antiperspirants upon first use and often require a number of applications over a period of time to reach a desired level of antiperspirant activity. The salts also tend to react with the skin and change its chemical composition. Therefore, work has been undertaken to discover compounds which will act rapidly to afford the desired antiperspirant activity, without the need for a series of applications to obtain useful antiperspirant effects. Of course, such products should also be harmless to clothing and the skin.
Anticholinergic compounds such as atropine and scopolamine have been used in the treatment of certain pathological cases of excessive perspiration. The eccrine sweat glands, which secrete most of the liquid sweat, are activated by a chemical "mediator" which is liberated at nerve endings when they are properly stimulated. This "mediator" is thought to be acetylcholine. Anticholinergic compounds reduce perspiration by interfering with the action of acetylcholine, probably by blocking the receptor sites of the secretory cells of the sweat glands.
Although the potential utility of anticholinergic compounds in over-the-counter antiperspirant formulations has long been recognized, such utilization has been retarded because the classic anticholinergics do not provide adequate inhibition of perspiration at a level of usage which is physiologically safe. Only recently have relatively safe and effective antiperspirant formulations based on anticholinergic compounds been investigated. Some such formulations, disclosed in British Pat. No. 940,279, contain certain anticholinergic scopolamine esters as active ingredients. Although the antiperspirant formulations of the British patent are said to be highly effective, the anticholinergic compounds employed therein can hydrolyze and the formulations thereby lose activity over protracted periods of time.
An improvement in the use of the scopolamine esters mentioned above is described in U.S. Pat. Nos. 3,312,709 and 3,326,768, in which para-(lower)alkoxybenzoyl esters of scopolamine or acid salts thereof are employed in compositions described as having improved anticholinergic and antiperspirant properties. Additional disclosures of antiperspirant formulations based on anticholinergic compounds are found in U.S. Pat. No. 3,624,200 and U.S. Pat. No. 3,767,786, also dealing with esters of scopolamine.
It is well known that anticholinergic compounds of the types discussed above have a mydriatic effect. This mydriatic effect, though desirable in conjunction with an eye examination by an eye doctor, is an undesirable property for an antiperspirant because an accidental transfer of an anticholinergic antiperspirant to the eye can represent a significant safety problem.
As exemplified by the above-mentioned U.S. patents, the predominant anticholinergics evaluated for antiperspirant use are scopolamine and its esters. Though the efficacy of scopolamine and its esters was demonstrated over twenty years ago, it is apparent that these compounds have not achieved widespread use as antiperspirants. This lack of use may be related to the mydriatic property referred to above, and, additionally, to the fact that ester-containing anticholinergics such as scopolamine may be cleaved by esterase activity in human perspiration, thus rendering the anticholinergic ineffective as an antiperspirant.
The problems of esterase inactivation and mydriasis, discussed above, have been overcome by the use of the novel glucuronide compounds of the subject invention.